KLK10 (Kallikrein-related peptidase 10)

2007-08-01   Liu-Ying Luo , Eleftherios P Diamandis 

R&D Systems, Inc. 614 McKinley Place, N. E. Minneapolis, MN 55413, USA (LYL); Department of Pathology, Laboratory Medicine, Mount Sinai Hospital, 600 University Ave. Toronto, ON M5G 1X5, Canada (EPD)





Spanning 5.7 kb of genomic DNA, the KLK10 gene consists of 5 introns and six exons.


The KLK10 gene has several splice variants with different lengths of the first exon. The predominant form is 1443 bp. Since the first exon is untranslated, all splice variants encode the same protein.


Not identified so far.



KLK10 is a 30 kDa serine protease containing 276 amino acids. It consists of a signal peptide (aa 1-33), an activation peptide (aa 34-42), and a mature chain (aa 43-276).


High levels of KLK10 expression are typically found in glandular epithelia in a wide variety of organs, such as salivary gland, gastrointestinal tract, prostate, lung, breast, and ovary.


KLK10 is synthesized as a precursor protein of 276 amino acids. Within the secretary pathway, its signal peptide is cleaved and it is secreted into the extracellular milieu as an inactive zymogen.
KLK10 has been identified in many biological fluids, such as blood, amniotic fluid, cerebrospinal fluid, milk, and nipple aspirate.


How KLK10 is activated remains undetermined. It is expected that upon activation, the peptide bond between arginine42 and lysine43 is proteolysed to release the mature chain. Mature KLK10 exhibits some typical characteristics of a trypsin-like serine protease, such as the catalytic triad (Histidine86, serine229, and aspartic acid137) and an aspartic acid in its substrate-binding pocket. However, its enzymatic activity has not been experimentally confirmed so far. Consequently, its potential physiologic substrates have not been identified.


Human KLK10 shares 98.2% and 69% identity with chimpanzee and mouse/rat klk10, respectively.



No germinal or somatic mutations are identified to be associated with cancer so far.

Implicated in

Entity name
Various cancers with upragulated KLK10.
Epithelial ovarian carcinoma, uterine serous papillary carcinoma, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and gastrointestinal tract cancer.
In these malignancies, KLK10 has been reported to be upregulated. Among them, epithelial ovarian carcinoma is by far studied the most. KLK10 is overexpressed in ovarian tumor tissue than in normal epithelium and stromal tissues both at the mRNA and protein levels. Due to increased leakage of KLK10 into the circulation, serum concentrations of KLK10 in ovarian cancer patients are elevated. High levels of KLK10 in tumor tissue or in serum are associated with more advanced disease stages and poor survival. In particular, preoperative serum KLK10 levels can serve as a complimentary biomarker for CA125, a well-established tumor marker routinely used in ovarian cancer. It has been demonstrated that nearly all CA125-negative tumors show KLK10 immunostaining positivity and that about 35% of CA125-negative patients have increased serum levels of KLK10. In combination with CA125, KLK10 can improve the diagnostic sensitivity by about 20% compared to that of CA125 alone.
No cytogenetic abnormalities are identified so far.
Hybrid gene
Not identified so far.
Entity name
Various cancers with down regulated KLK10.
Breast cancer, testicular cancer, leukemia, and prostate cancer.
In contrast to ovarian cancer, KLK10 is down regulated in these malignancies, with breast cancer as a prototype. Several lines of evidence have demonstrated that KLK10 is progressively down regulated during breast cancer development. In a clinical study, it is observed that essentially all normal breast specimens had KLK10 expression, whereas about 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) had no detectable KLK10 expression. More importantly, the KLK10 negative-DCIS was found to subsequently develop to IDC. In in vitro studies, it has been shown that KLK10 is expressed in normal breast epithelial cells but dramatically reduced in breast cancer cell lines. Moreover, reintroduction of KLK10 expression into these cancer cells can suppress their tumorigenecity in nude mice. KLK10 was thus considered to function as a tumor suppressor in breast cancer. The mechanisms governing the down regulation of KLK10 in breast cancer is not clear. One explanation is CpG island hypermethylation of exon 3, as demonstrated in a number of cancer cell lines. Noteworthy, expression of KLK10 is modulated by some steroid hormones and retinoid acid. They may, under certain conditions, also contribute to the aberrant expression of KLK10 in tumor tissues. However, the paradoxical expression of KLK10 in different types of tumors remains obscure.


Pubmed IDLast YearTitleAuthors
163215662006Identification of molecular targets for immunotherapy of patients with head and neck squamous cell carcinoma.Dasgupta S et al
117058532001Analysis of normal epithelial cell specific-1 (NES1)/kallikrein 10 mRNA expression by in situ hybridization, a novel marker for breast cancer.Dhar S et al
169282232006Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.Feng B et al
98099761998The role for NES1 serine protease as a novel tumor suppressor.Goyal J et al
171821772007Downregulation and CpG island hypermethylation of NES1/hK10 gene in the pathogenesis of human gastric cancer.Huang W et al
116918272001CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression.Li B et al
87641361996Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression.Liu XL et al
96477361998Structural characterization and mapping of the normal epithelial cell-specific 1 gene.Luo L et al
145681872003Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter.Luo LY et al
125917302003The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis.Luo LY et al
114610802001Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue.Luo LY et al
121852032002Human kallikrein 10 expression in normal tissues by immunohistochemistry.Petraki CD et al
146280742004The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3-4, is downregulated by hypermethylation in acute lymphoblastic leukemia.Roman-Gomez J et al
160612772005Potential markers that complement expression of CA125 in epithelial ovarian cancer.Rosen DG et al
166479132006Overexpression of kallikrein 10 (hK10) in uterine serous papillary carcinomas.Santin AD et al
128213402003Overexpression of kallikrein 10 in epithelial ovarian carcinomas.Shvartsman HS et al
162544622005Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.Sidiropoulos M et al
175049902007A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma.Vachani A et al
161037442005Identification of new splice variants and differential expression of the human kallikrein 10 gene, a candidate cancer biomarker.Yousef GM et al
127881702003Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery.Yunes MJ et al
168007352006The human kallikrein 10 promoter contains a functional retinoid response element.Zeng M et al

Other Information

Locus ID:

NCBI: 5655
MIM: 602673
HGNC: 6358
Ensembl: ENSG00000129451


dbSNP: 5655
ClinVar: 5655
TCGA: ENSG00000129451


Gene IDTranscript IDUniprot

Expression (GTEx)



Pubmed IDYearTitleCitations
200861752010Smad signaling is required to maintain epigenetic silencing during breast cancer progression.74
204241352010Blood biomarker levels to aid discovery of cancer-related single-nucleotide polymorphisms: kallikreins and prostate cancer.29
190858362009Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity.17
228741022012Quantitative DNA methylation analysis of genes coding for kallikrein-related peptidases 6 and 10 as biomarkers for prostate cancer.17
234995832013Clinical significance of kallikrein-related peptidase (KLK10) mRNA expression in colorectal cancer.16
162544622005Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.14
206803162011The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer.13
188548342008Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma.11
197606082009Aberrant DNA methylation profile and frequent methylation of KLK10 and OXGR1 genes in hepatocellular carcinoma.11
120874682002Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resistance.10


Liu-Ying Luo ; Eleftherios P Diamandis

KLK10 (Kallikrein-related peptidase 10)

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/gene/41076/klk10